Dataset Information

Nuclear receptor HNF4? binding sequences are widespread in Alu repeats.

ABSTRACT:

Background

Alu repeats, which account for ~10% of the human genome, were originally considered to be junk DNA. Recent studies, however, suggest that they may contain transcription factor binding sites and hence possibly play a role in regulating gene expression.

Results

Here, we show that binding sites for a highly conserved member of the nuclear receptor superfamily of ligand-dependent transcription factors, hepatocyte nuclear factor 4alpha (HNF4?, NR2A1), are highly prevalent in Alu repeats. We employ high throughput protein binding microarrays (PBMs) to show that HNF4? binds > 66 unique sequences in Alu repeats that are present in ~1.2 million locations in the human genome. We use chromatin immunoprecipitation (ChIP) to demonstrate that HNF4? binds Alu elements in the promoters of target genes (ABCC3, APOA4, APOM, ATPIF1, CANX, FEMT1A, GSTM4, IL32, IP6K2, PRLR, PRODH2, SOCS2, TTR) and luciferase assays to show that at least some of those Alu elements can modulate HNF4?-mediated transactivation in vivo (APOM, PRODH2, TTR, APOA4). HNF4?-Alu elements are enriched in promoters of genes involved in RNA processing and a sizeable fraction are in regions of accessible chromatin. Comparative genomics analysis suggests that there may have been a gain in HNF4? binding sites in Alu elements during evolution and that non Alu repeats, such as Tiggers, also contain HNF4? sites.

Conclusions

Our findings suggest that HNF4?, in addition to regulating gene expression via high affinity binding sites, may also modulate transcription via low affinity sites in Alu repeats.

SUBMITTER: Bolotin E

PROVIDER: S-EPMC3252374 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Publications

Nuclear receptor HNF4α binding sequences are widespread in Alu repeats.

Bolotin Eugene E Chellappa Karthikeyani K Hwang-Verslues Wendy W Schnabl Jake M JM Yang Chuhu C Sladek Frances M FM

BMC genomics 20111115

<h4>Background</h4>Alu repeats, which account for ~10% of the human genome, were originally considered to be junk DNA. Recent studies, however, suggest that they may contain transcription factor binding sites and hence possibly play a role in regulating gene expression.<h4>Results</h4>Here, we show that binding sites for a highly conserved member of the nuclear receptor superfamily of ligand-dependent transcription factors, hepatocyte nuclear factor 4alpha (HNF4α, NR2A1), are highly prevalent in ...[more]

PMID: 22085832

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